Sympathetic Regulation of Hematopoiesis and the Mobilization of Inflammatory Cells in ICR Mice with Traumatic Brain Injury: A Novel Approach to Targeting Neuroinflammation and Degenerative Processes

<b>Background/Objectives</b>: Neuroinflammation is a leading factor in secondary brain damage following a traumatic brain injury (TBI). Existing therapeutic approaches have limited efficacy against neuroinflammation. The bone marrow, the primary hematopoietic organ, is also a source of inflammatory cells. We propose that targeting the sympathetic regulation of inflammatory cell mobilization could reduce neuroinflammation after TBI. <b>Methods</b>: In ICR mice, we investigated the immune cell response in the blood, bone marrow, motor cortex, and the subventricular zone after TBI modeling and treatment with the sympatholytic agent reserpine. <b>Results</b>: TBI induced neutrophilia and lymphocytosis in the peripheral blood, activated hematopoiesis in the bone marrow, and triggered neuroinflammation and degenerative changes in the cerebral cortex (CC) and the subventricular zone (SVZ) of mice. Reserpine reduced leukocytosis in the blood and hematopoietic activity in the bone marrow of mice with TBI compared to untreated TBI mice. Furthermore, reserpine decreased neutrophilic and lymphocytic infiltration, as well as the number of Iba1⁺ microglial cells, including M1-polarized microglia, Caspase-3⁺ cells, and cells expressing myeloperoxidase (MPO) in the CC and SVZ of treated mice. The activity of degenerative processes was also reduced. Additionally, reserpine reduced the number of M2-polarized microglial cells in the SVZ. <b>Conclusions</b>: The sympatholytic drug reserpine may hold promise for the development of a novel approach to treating neuroinflammation and degeneration following a TBI. This is based on its ability to reduce hematopoiesis and mobilize inflammatory cells from the bone marrow into the bloodstream.